Australian Stroke Genetics Collaborative - Genome-wide Association Study In Ischaemic Stroke
Funder
National Health and Medical Research Council
Funding Amount
$1,141,037.00
Summary
The majority of stroke is caused by atherothrombosis, the formation of blood clots in brain blood vessels. Numerous genes are linked to atherothrombosis, but many studies examined genetic influences in isolation from environmental risk factors. We will examine the relevance of genetic variations linked to atherothrombosis, in the context of environmental risk factors. By determining the contribution of genetic and environmental factors in stroke, we will develop a stroke risk assessment tool.
Accurate Prediction Of Individual Risk To Disease From Genome-wide Association Studies
Funder
National Health and Medical Research Council
Funding Amount
$269,371.00
Summary
Risk for many complex diseases (such as psychiatric disorders or heart disease) has a substantial genetic component, however few specific high risk variants have been identified. Evidence is mounting that there are likely to be hundreds of risk loci each individually conferring a very low increase in relative risk for disease. We aim to develop methods that utilise information from multiple genetic risk variants simultaneously to create a 'genomic profile' of risk.
Identification Of A Gene That Increases Risk Of MS Via A Pathway Involving UV Exposure
Funder
National Health and Medical Research Council
Funding Amount
$111,000.00
Summary
Multiple sclerosis (MS) is an auto-immune disease of the central nervous system that affects over 10 000 Australians. It is a progressive debilitating disease that affects predominantly young adults and current therapies are expensive, only moderately effective and are associated with significant side effects. The biological processes leading to this disease are not well understood and there is a need to identify new ways of treating the disease or preventing it. One of the known factors associa ....Multiple sclerosis (MS) is an auto-immune disease of the central nervous system that affects over 10 000 Australians. It is a progressive debilitating disease that affects predominantly young adults and current therapies are expensive, only moderately effective and are associated with significant side effects. The biological processes leading to this disease are not well understood and there is a need to identify new ways of treating the disease or preventing it. One of the known factors associated with MS is the striking association of increased MS incidence with cooler climates and reduced sun exposure. A study conduced by the Menzies Centre has recently provided evidence that increased childhood sun exposure is significantly associated with reduced risk of MS. This project aims to study those genes involved in the body's response to sun exposure as we propose that if sun exposure influences risk of MS then those genes may interact with sun exposure to modify risk of MS.Read moreRead less
KILLING OF MYCOBACTERIUM TUBERCULOSIS IN MACROPHAGES VIA THE P2X7 RECEPTOR
Funder
National Health and Medical Research Council
Funding Amount
$226,320.00
Summary
Tuberculosis remains an enormous global health problem. Some 32% of the world population are infected, with over 1 million persons dying each year. The risk of an infected individual developing clinical disease ranges from 2-23% for their lifetime. We know that both environmental factors, such as declining socio-economic conditions, and genetic risk factors such as HLA type contribute to the likelihood of an individual developing disease, but current known factors are insufficient to fully accou ....Tuberculosis remains an enormous global health problem. Some 32% of the world population are infected, with over 1 million persons dying each year. The risk of an infected individual developing clinical disease ranges from 2-23% for their lifetime. We know that both environmental factors, such as declining socio-economic conditions, and genetic risk factors such as HLA type contribute to the likelihood of an individual developing disease, but current known factors are insufficient to fully account for the risk attributed to genetics. The aim of this project is to investigate another potential risk factor involved in the development of tuberculosis, that of P2X7 receptor function. A natural compound, ATP, when added to macrophages is able to kill tuberculosis organisms residing within the macrophage. This process occurs when ATP activates the P2X7 receptor. We have recently identified a mutation in the P2X7 receptor, which causes a loss of receptor function. Individuals who have this mutation are unable to respond to ATP and hence may be unable to kill tuberculosis. Our studies will determine if the mutation we have identified in the P2X7 receptor prevents or inhibits ATP mediated killing of mycobacteria. Furthermore we will determine the frequency of this mutation in TB patients and the general population to determine if this mutation in the P2X7 receptor is a risk factor for the development of tuberculosis disease.Read moreRead less
Risk Factors For The Development Of Eating Disorder Phenotypes And Endophenotypes In Adolescent Twins
Funder
National Health and Medical Research Council
Funding Amount
$266,500.00
Summary
The overall aim of the project is to develop a better understanding of how environment, temperament and genes work together to cause disordered eating and eating disorders. Eating disorders, including anorexia nervosa and bulimia nervosa, are an extremely difficult and costly condition to treat, and are associated with high mortality. Eating disorders in adolescence lead to increased risk for anxiety disorders, chronic fatigue, chronic pain, depressive disorders, infectious diseases, suicide att ....The overall aim of the project is to develop a better understanding of how environment, temperament and genes work together to cause disordered eating and eating disorders. Eating disorders, including anorexia nervosa and bulimia nervosa, are an extremely difficult and costly condition to treat, and are associated with high mortality. Eating disorders in adolescence lead to increased risk for anxiety disorders, chronic fatigue, chronic pain, depressive disorders, infectious diseases, suicide attempts, and limitation in activities due to poor health in adulthood. Full- and partial-syndrome eating disorders affect around 10% of adolescent girls. Given the seriousness of the consequences of eating disorders, and the large number of Australians affected, a better understanding of what causes the development of eating disorders is required. The current research investigates identical and non-identical adolescent female twins aged 13-15 years. As well as examining their eating, this study will look at the sort of environments and temperaments that may increase genetic susceptibility to develop eating problems. The types of environment to be examined include media influence, weight related peer teasing, parental dieting, and pre- and pernatal complications. Twin temperament will also be examined, including perfectionism, sense of ineffectiveness, body dissatisfaction and depression. Parental anxiety and novelty seeking will also be examined for impact on the development of disordered eating in their children. The twins will be followed up over a 2-year period, the peak risk age for onset of eating problems. By comparing the identical and non-identical twins, we can define the characteristics of those most at risk of developing eating problems. The results of this project can be used to formulate specific prevention strategies.Read moreRead less
Linkage And Sequence Analysis Of A Locus On The X Chromosome That Contributes To Population Variation In Blood Pressure
Funder
National Health and Medical Research Council
Funding Amount
$458,080.00
Summary
High blood pressure is a prominent risk factor for heart attack and stroke which kill over 30,000 Australians each year. Blood pressure is determined by the combination of inherited predisposition and lifestyle factors such as diet. Understanding these combinations offers new opportunities for reducing the incidence of cardiovascular disease. We have discovered recently that genes on the sex chromosome known as chromosome X appear to be linked with high blood pressure. Building on this basic obs ....High blood pressure is a prominent risk factor for heart attack and stroke which kill over 30,000 Australians each year. Blood pressure is determined by the combination of inherited predisposition and lifestyle factors such as diet. Understanding these combinations offers new opportunities for reducing the incidence of cardiovascular disease. We have discovered recently that genes on the sex chromosome known as chromosome X appear to be linked with high blood pressure. Building on this basic observation, we shall extend our studies to place the findings beyond reasonable doubt. We shall investigate the gene sequences in this region of the X chromosome to discover what changes in the DNA code might lead to high blood pressure and how this might happen. Our studies capitalise on the recent release of the draft sequence of the entire human genome. These investigations in almost 800 healthy volunteer families have the potential to provide new opportunities for prevention and treatment of cardovascular disease.Read moreRead less
Germline Mutations In Mismatch Repair Genes: Prevalence, Risk Of Cancer, And Environmental Modifiers Of Risk.
Funder
National Health and Medical Research Council
Funding Amount
$216,750.00
Summary
Aims: 1. Develop a model that will predict who has a mutation in a group of genes that cause cancer 2. Estimate risk of cancer in people who have a mutation in these genes (carriers) 3. Determine if cancer risk in carriers can be reduced People who inherit a mutation in a group of genes called 'mismatch repair genes' are at increased risk of cancer, particularly cancer of the colon and rectum. If these carriers can be identified they can take preventive measures such as screening to reduce their ....Aims: 1. Develop a model that will predict who has a mutation in a group of genes that cause cancer 2. Estimate risk of cancer in people who have a mutation in these genes (carriers) 3. Determine if cancer risk in carriers can be reduced People who inherit a mutation in a group of genes called 'mismatch repair genes' are at increased risk of cancer, particularly cancer of the colon and rectum. If these carriers can be identified they can take preventive measures such as screening to reduce their risk of cancer and death. We will develop a model using data from the Colon Cancer Family Registry (CFR), the world's largest dataset of carriers and non-carriers which has already recruited and genetically tested over 4,000 families from Australasia, USA and Canada. The model will allow clinicians to predict who is a likely be a carrier based so they can be tested for the mutation. We know the risk of cancer is high in carriers, but we don't have precise estimates. We will use the Colon CFR applying sophisticated statistical methods required to answer this question. This data is critical for genetic counselling so appropriate decisions can be made by the patient and the doctor as to what preventive measures to take. We will also use the Colon CFR data to find out what how the carriers who develop cancer differ from those who stay cancer free using their completed lifestyle questionnaires which includes questions on diet, smoking, alcohol consumption, exercise, aspirin use, and oral contraceptive pill use. We may identify risk factors that carriers can avoid (or take up if they reduce cancer risk) to reduce their risk of cancer.Read moreRead less
Linkage And Association Analyses Of A Locus On Chromosome 4 That Contributes To Population Variation In HDL Cholesterol
Funder
National Health and Medical Research Council
Funding Amount
$372,562.00
Summary
High-density lipoprotein (HDL) cholesterol is also known as good cholesterol becuase it helps remove cholesterol from the body. Many studies have shown that the higher one's HDL cholesterol, the less likely is the development of hardening of the arteries and heart attack. The important questions are what controls HDL cholesterol levels and how could we make them higher? We know that lifestyle and genetics are important. Smoking and lack of exercise are known to reduce HDL cholesterol, while mode ....High-density lipoprotein (HDL) cholesterol is also known as good cholesterol becuase it helps remove cholesterol from the body. Many studies have shown that the higher one's HDL cholesterol, the less likely is the development of hardening of the arteries and heart attack. The important questions are what controls HDL cholesterol levels and how could we make them higher? We know that lifestyle and genetics are important. Smoking and lack of exercise are known to reduce HDL cholesterol, while moderate alcohol intake increases HDL cholesterol. However, genetic factors are very important determinants, but have remained obscure. Through our recent discovery in the Victorian Family Heart Study (VFHS), we located a region on chromosome 4 that influences plasma level of HDL cholesterol. Further testing has confirmed and refined our genetic target - a gene somewhere in this region that controls HDL cholesterol levels. The next step is to find the culprit gene and the DNA sequences that explain why some people have high and others low HDL cholesterol levels. We have the advantage of a large and well characterised group of volunteers and the very latest molecular techniques to track down the gene. Few other groups internationally have our resources or are as advanced in their research. This study will have significant implications for the development of effective and targeted strategies for detection, prevention and treatment of cardiovascular disease.Read moreRead less
Novel Statistical Methods For The Analysis Of Meausred Genetic And Environmental Risk Factors In Twin Studies
Funder
National Health and Medical Research Council
Funding Amount
$478,314.00
Summary
Studies on twins are an important way to determine whether the risk of disease is likely to be influenced by genetic factors but have traditionally focussed on unmeasured factors. New epidemiological studies measure thousands of genetic variants on many participants. This project will extend methods for analysing data within and between twin pairs to determine whether risk factors are likely to be causal and therefore should be the subject of further designed studies based on intervention.